For many diseases, cell therapy—implanting living cells within the body—could be a simple, low risk, and cost-effective alternative to whole organ replacement. These types of therapies could also allow efficient use of donor organs, which are in critically short supply. Further, while use of human tissues can clearly prevent problems with rejection of the cells, there is an interest in developing cellular devices that could also utilize cells from other animals such as pigs.
One area of interest is the implantation of pancreatic islets into patients suffering from Type I diabetes in order to produce insulin. A properly designed device could allow for close control over the release of insulin, thereby allowing good regulation of blood glucose levels.
Cell therapy using autologous (self) or mismatched (allogeneic, xenogeneic) cells is likely to succeed clinically only if cells survive at the transplantation site and are protected against immune rejection. Many cell transplantation techniques have been introduced over the years to achieve these objectives, only to be discarded after more careful evaluation and data analysis.
With regard to rejection, encapsulation has been shown to allow transplantation of cells without immunosuppression. In this technique, cells are surrounded by a semipermeable membrane that allows free exchange of oxygen, nutrients, and metabolites while preventing the passage of cells and high molecular weight substances such as immunocytes, antibodies, and complement factors.
However, several limitations exist in implementing such therapy. For example, cell survival depends on nutrient and oxygen availability at the transplantation site. The latter may require neovascularization at the implantation site, a process that requires a significant amount of time. Further, cellular devices may exhibit breakage after several weeks of transplantation and/or an immunosuppressive response, thereby limiting longer term viability and/or retrieval of the devices.
In addition, use of cells from non-human donors presents additional challenges. Porcine tissues and cells are known to be infected with endogenous retroviruses. The genomes of all domesticated swine species tested thus far contain multiple integrated copies of an endogenous C-type retrovirus termed porcine endogenous retrovirus (PERV). Transmission of xenogeneic retroviral infections to xenograft recipients is of particular concern because retroviruses are known to result in lifelong persistent infections. Development of improved cellular devices is, therefore, of interest, which might then reduce or eliminate the risk of PERV contamination and allow the use of cellular material from pigs for various therapeutic uses.
Accordingly, there is an existing need to develop new cellular devices for use in implanting various types of cells without these associated risks and disadvantages. This invention addresses these needs and others.